Diallyl disulfide ameliorates isoproterenol induced cardiac hypertrophy activating mitochondrial biogenesis via eNOS-Nrf2-Tfam pathway in rats

二烯丙基二硫化物通过 eNOS-Nrf2-Tfam 通路激活大鼠线粒体生物合成,改善异丙肾上腺素诱导的心脏肥大

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作者:Tarak Nath Khatua, Amit K Dinda, Uday K Putcha, Sanjay K Banerjee

Abstract

The beneficial effect of garlic on cardiovascular disease is well known. However, the use of raw garlic against cardiac hypertrophy is not established. In the present study we explored whether raw garlic and its compound, diallyl disulfide (DADS) could inhibit hypertrophy through H2S and/or mitochondrial biogenesis. Cardiac hypertrophy was induced in rat by giving isoproterenol at the dose of 5 mg/kg/day subcutaneously for 14 days through alzet minipump. Aqueous garlic homogenate, DADS and NaHS (liberate H2S) were fed to third, forth and fifth group of rats for 14 days at a dose of 250 mg/kg/day, 50 mg/kg/day, 14 µM/kg/day respectively. Garlic and DADS reduced cardiac hypertrophy markers and normalized mitochondrial ETC-complex activities, mitochondrial enzyme activites and mitochondrial biogenetic and apoptotic genes expression. Garlic and DADS enhanced eNOS and p-AKT level in rat heart along with increased NRF2 protein level and Tfam gene expression. However, normalization was not observed after administration of NaHS which generates H2S in-vivo. In conclusion, garlic and DADS induces mitochondrial biogenesis and ameliorates cardiac hypertrophy via activation of eNOS-Nrf2-Tfam pathway in rats.

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